WO 2006/116764 published 2 Nov. 2006, incorporated by reference in its entirety, describes various compounds and detailed synthetic schemes for their preparation. In particular, a reaction sequence is depicted at page 79 thereof wherein 3-benzyloxy-2-methyl-1H-pyridine-4-one of formula 3 is there brominated to the bromopyridine 4 there, which is then reacted with methanol and carbon monoxide to yield the nicotinic acid methyl ester 5 there which is after several steps reacted with a benzylamine to create the amide side chain-containing pyridine 10. Thus, the amide sidechain is in place before creation of the Z1Z2 ring of the final product formula (I) therein in the reaction depicted at page 80 from 16 to 17-1.
A second reaction sequence is depicted at page 113 of WO 2006/116764 wherein a pyrrolidine compound 102 is allowed to condense into a tricyclic compound 103 which is then brominated to yield the bromine compound 104 which is then reacted with a benzylamine to create the amide side chain-containing tricyclic compound 105 therein. Thus, the bromination takes place after creation of the Z1Z2 ring of the final product of formula (I) therein.
N-Methoxy-N-methyl amides may be prepared by Pd catalyzed aminocarbonylation of aryl bromides as described by J. R. Martinelli et al in Organic Letters, Vol. 8, No. 21, pages 4843-4846 (2006). Bromoanilines and bromoanisoles are converted to esters as described by J. Albaneze-Walker et al in Organic Letters, Vol. 6, No. 13, pages 2097-2100 (2004).